Randomized Blinded Discontinuation Trial of Ocrelizumab in Early Relapsing Multiple Sclerosis

The primary study objective is to evaluate the rate of durable remission of relapsing disease activity, assessed serially both clinically and by MRI, from randomization through 48 months in participants with early relapsing multiple sclerosis who discontinue OCR after 12 and 24 months of treatment. Secondary objectives include: - Mechanistic: To compare the ratios of pro-inflammatory and anti-inflammatory B cells at Month 48 in participants who do versus do not experience durable remission of relapsing disease activity after discontinuation of OCR - Efficacy: 1. To evaluate the incidence of relapsing disease activity through 48 months in participants with early relapsing multiple sclerosis who receive ongoing OCR treatment 2. To evaluate the magnitude of change in EDSS through 48 months in participants with early RMS who discontinue OCR after 12 and 24 months of treatment and in those who receive ongoing OCR treatment - Safety: To describe the effect of discontinuation of OCR and ongoing OCR on measures of safety and drug related toxicities - Exploratory: 1. To evaluate the magnitude of change in the following disease-specific assessments and PROs through 48 months in participants with early RMS who do or do not experience durable remission of relapsing disease activity after discontinuation of OCR, and those who receive ongoing OCR treatment: o Symbol Digit Modalities Testing (SDMT), o Low Contrast Letter Acuity (LCLA), o Modified Fatigue Impact Scale (MFIS), o Multiple Sclerosis Quality of Life 54 Instrument (MSQOL-54), o Patient Health Questionnaire - 9 (PHQ9), and o EuroQol-5 Dimension-5 Level Instrument (EQ-5D-5L) 2. To evaluate NfL levels in participants with early RMS who do or do not experience durable remission of relapsing disease activity after discontinuation of OCR, and those who receive ongoing OCR treatment 3. To evaluate B cell levels in participants with early RMS who do or do not experience durable remission of relapsing disease activity after discontinuation of OCR, and those who receive ongoing OCR treatment 4. To compare the longitudinal profiles of cellular immune functions in participants who do versus do not experience durable remission of relapsing disease activity after discontinuation of OCR 5. To evaluate whether cellular immune functions at baseline and changes from baseline to three months are predictive of whether participants do or do not experience durable remission of relapsing disease activity after discontinuation of OCR 6. To assess the profile of cellular immune functions in samples collected most proximate to new relapsing disease activity, in those individuals who do not experience durable remission The primary outcome variable is durable disease remission of relapsing disease activity, defined as the absence of new relapsing disease activity from randomization through Month 48. This includes absence of clinical relapse as well as absence of new or enlarging T2 lesions on all serial follow up scans. Secondary outcome variables include: - Mechanistic: The ratio of granulocyte macrophage colony-stimulating factor (GM-CSF) expressing to IL-10 expressing B cells at Month 48 in participants who do versus do not exhibit durable disease remission - Efficacy: The change in EDSS score from the Month 12 Visit - Safety: 1. The proportion of participants with a SAE, as defined in Section 12.2.4. 2. The proportion of participants who experience at least one Grade 3 or higher adverse event using National Cancer Institutes Common Terminology Criteria for Adverse Events NCI-CTCAE version 5.0 3. The proportion of participants with the following adverse events: o Infections, Grade 3 or higher o Malignancies 4. The proportion of participants experiencing infusion related reactions, defined as any at least possibly related adverse reaction within 24 hours of i

You may be eligible for this study if you meet the following criteria:

• Conditions:
  Medical Research
• Age: - 99 Years
• Gender: All